This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in subjects with advanced solid tumors followed by an expansion phase in patients with advanced solid tumors. An exploration cohort has been added to determine the safety using Q4W dosing.

Anti-tumor efficacy (dose expansion subjects) [ Time Frame: Until end of study ]

Evaluate the objective response rate in subjects with non-squamous NSCLC who have received 2 or more prior lines of therapy and subjects with squamous NSCLC who have received 1 prior lines of therapy and 2 or more prior lines of therapy

Secondary Outcome Measures:

Area under the concentration time curve, maximum concentration, clearance, half-life after administration of MEDI4736. [ Time Frame: Up to 90 days after the last dose of MEDI4736 ]

Number and percentage of subjects who develop detectable anti-drug antibodies (ADAs). [ Time Frame: Up to 6 months after the last dose of MEDI4736. ]

The immunogenic potential of MEDI4736 will be assessed by summarizing the number and percentage of subjects who develop detectable anti-drug antibodies (ADAs).

Objective response rate (ORR) [ Time Frame: Until end of study ]

The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR

Disease control rate (DCR) [ Time Frame: Until end of study ]

The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for

≥ 12 weeks)

Duration of response (DR) [ Time Frame: Until end of study ]

Duration of response will be defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.

Progression-free survival (PFS) [ Time Frame: Until end of study ]

Progression-free survival is the time interval from the start of treatment with MEDI4736 until the documentation of confirmed immune-related disease progression or death due to any cause, whichever occurs first.

Overall survival (OS) [ Time Frame: From first dose of study drug until death or up to 2 years ]

Overall survival will be determined as the time from the start of treatment with MEDI4736 until death.

MEDI4736 will be administered by IV infusion every 14, 21, or 28 days.

Other Name: Durvalumab

Experimental: MEDI4736 Q3W

Evaluate MEDI4736 given every 3 weeks

Drug: MEDI4736

MEDI4736 will be administered by IV infusion every 14, 21, or 28 days.

Other Name: Durvalumab

Experimental: MEDI4736 Dose Expansion

At least 16 different types of solid tumors will be evaluated in the expansion phase

Drug: MEDI4736

MEDI4736 will be administered by IV infusion every 14, 21, or 28 days.

Other Name: Durvalumab

Experimental: MEDI4736 Q4W

Evaluate MEDI4736 given every 4 weeks

Drug: MEDI4736

MEDI4736 will be administered by IV infusion every 14, 21, or 28 days.

Other Name: Durvalumab

Detailed Description:

A dose-escalation and dose-expansion study of MEDI4736 (a monoclonal antibody that targets programmed cell death-1 ligand 1 (PD-L1)) will evaluate the safety, tolerability, PK, IM, and antitumor activity of MEDI4736 in adult patients with solid tumors. A dose exploration cohort will look at the safety profile of Q4W dosing of MEDI4736.

Eligibility

Ages Eligible for Study:

18 Years to 99 Years (Adult, Senior)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Age 18 or older.

In the dose-escalation phase: histologically- or cytologically- confirmed advanced solid tumor that is refractory to standard therapy and for which no standard therapy exists.

In the dose-expansion phase: histologically- or cytologically- confirmed advanced solid tumor where if an approved first-line therapy is available, subjects must have failed, be intolerant to, be ineligible for, or have refused

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To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01693562